التفاصيل البيبلوغرافية
| العنوان: |
Localization and Processing of the Amyloid-β Protein Precursor in Mitochondria-Associated Membranes. |
| المؤلفون: |
Debayle, Delphine, Gay, Anne Sophie, Bussiere, Renaud, Bauer, Charlotte, Checler, Frederic, Chami, Mounia, Del Prete, Dolores, Wieckowski, Mariusz R., Suski, Jan M., Lacas-Gervais, Sandra, Oulès, Bénédicte, Pinton, Paolo, Paterlini-Bréchot, Patrizia, Checler, Frédéric |
| المصدر: |
Journal of Alzheimer's Disease; 2017, Vol. 55 Issue 4, p1549-1570, 22p |
| مصطلحات موضوعية: |
ALZHEIMER'S disease, AMYLOID beta-protein precursor, MITOCHONDRIAL membranes, ENDOPLASMIC reticulum, PROTEOMICS, LIPIDS, TRIGLYCERIDES, BRAIN function localization, CALCIUM metabolism, ENZYME metabolism, ANIMAL experimentation, ANIMALS, CELL lines, CELL membranes, ELECTRON microscopy, ENZYME inhibitors, GENES, GENETIC techniques, HETEROCYCLIC compounds, MASS spectrometry, MEMBRANE proteins, MICE, MITOCHONDRIA, GENETIC mutation, NEUROBLASTOMA, PEPTIDES, PROTEIN precursors, PROTEOLYTIC enzymes, QUINOLINE, RODENTS, PRECIPITIN tests, PHARMACODYNAMICS |
| مستخلص: |
Alteration of mitochondria-associated membranes (MAMs) has been proposed to contribute to the pathogenesis of Alzheimer's disease (AD). We studied herein the subcellular distribution, the processing, and the protein interactome of the amyloid-β protein precursor (AβPP) and its proteolytic products in MAMs. We reveal that AβPP and its catabolites are present in MAMs in cellular models overexpressing wild type AβPP or AβPP harboring the double Swedish or London familial AD mutations, and in brains of transgenic mice model of AD. Furthermore, we evidenced that both β- and γ-secretases are present and harbor AβPP processing activities in MAMs. Interestingly, cells overexpressing APPswe show increased ER-mitochondria contact sites. We also document increased neutral lipid accumulation linked to Aβ production and reversed by inhibiting β- or γ-secretases. Using a proteomic approach, we show that AβPP and its catabolites interact with key proteins of MAMs controlling mitochondria and ER functions. These data highlight the role of AβPP processing and proteomic interactome in MAMs deregulation taking place in AD. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
